Combined enzyme defect of mitochondrial fatty acid oxidation

A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and car...

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Bibliographic Details
Published in:The Journal of clinical investigation 1992-10, Vol.90 (4), p.1219-1225
Main Authors: JACKSON, S, RAJINDER SINGH KLER, BARTLETT, K, BRIGGS, H, BINDOFF, L. A, POURFARZAM, M, GARDNER-MEDWIN, D, TURNBULL, D. M
Format: Article
Language:English
Subjects:
3-Hydroxyacyl CoA Dehydrogenases - deficiency
Adult
Biological and medical sciences
Child, Preschool
Diseases of striated muscles. Neuromuscular diseases
Enoyl-CoA Hydratase - deficiency
Fatty Acids - metabolism
Female
Humans
Lipid Metabolism, Inborn Errors - enzymology
Male
Medical sciences
Mitochondria - enzymology
Muscular Diseases - etiology
Neurology
Oxidation-Reduction
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Summary:A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci115983